Antibiotics may not be enough to stop recurrent gastric lymphoma caused by Helicobacter pylori
Research led by Dr. Anne Mueller at Stanford University School of Medicine demonstrates that successful eradication of Helicobacter may not prevent future aggressive gastric lymphoma since resting B cells are left behind. The paper by Mueller et al., "The role of antigenic drive and tumor-infiltrating accessory cells in the pathogenesis of Helicobacter-induced MALT lymphoma," appears in the September issue of The American Journal of Pathology.
Helicobacter pylori, a spiral bacterium of the stomach, infects more than half of the world’s population. It is now widely accepted that, aside from gastritis and ulcers, H. pylori is also a causative agent of gastric lymphoma, specifically gastric B cell lymphoma of mucosa-associated lymphoid tissue (MALT). While antibiotic treatment eradicates the bacteria and promotes tumor regression, the effects of re-infection on disease are more severe.
To address the effects of re-infection and the role of immune cells in disease progression, Dr. Mueller’s group used a mouse model of Helicobacter-induced MALT lymphoma that employs H. felis to mimic human disease in the mouse. Mice were infected with H. felis and maintained for 18 months before being assigned to one of three treatment groups: 1) no treatment (primarily infected), 2) antibiotic therapy to eradicate bacteria, or 3) antibiotic therapy followed by re-infection.
As expected, low-grade MALT lymphoma occurred in 35% of all infected animals. However, frank MALT lymphoma was more prevalent in re-infected animals (44%) than in primarily infected animals (25%). Transcription profiling identified B cell markers in mice that had been infected at any point in time, even after successful antibiotic treatment, suggesting that resting B cells remain in the gastric mucosa.
Lymphoid aggregates of re-infected animals also contained more proliferating cells than those of primarily infected or antibiotic-treated animals (46% vs. 23.2% or 4.8%, respectively). Closer inspection of the lymphoid aggregates revealed that the tumors were indeed derived from B cells and the main antigen-presenting cells were follicular dendritic cells. Finally, follicular dendritic cell numbers were highest in the tumors of re-infected animals followed by primarily infected and then antibiotic-treated animals, thus correlating with severity of gastric lymphoma.
Because it is the follicular dendritic cells that present antigen to T cells that in turn activate B cell proliferation, follicular dendritic cells appear to be better indicators of tumor behavior than B cells. Thus, follicular dendritic cells represent an untapped target in the fight against recurrent gastric lymphoma.
The significance of the described work is that gastric lymphoma progresses more rapidly upon secondary infection. Because resting B cells are left behind following antibiotic treatment, re-infection by H. pylori promotes the existing B cells to progress quickly into tumors. Therefore, it is important that treated patients be carefully monitored for H. pylori re-infection.
Audra Cox | EurekAlert!
The most recent press releases about innovation >>>
Die letzten 5 Focus-News des innovations-reports im Überblick:
For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.
In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...
Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale
Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...
For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.
But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...
Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.
The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...
Theoretical physicists propose to use negative interference to control heat flow in quantum devices. Study published in Physical Review Letters
Quantum computer parts are sensitive and need to be cooled to very low temperatures. Their tiny size makes them particularly susceptible to a temperature...